Growth enhancement in suppressor of cytokine signaling 2 (SOCS-2)-deficient mice is dependent on signal transducer and activator of transcription 5b (STAT5b)
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Mice lacking suppressor of cytokine signaling-2 (SOCS-2) exhibit accelerated postnatal growth resulting in adult mice that are 1.3 to 1.5 times the size of normal mice. In this study we examined the somatotrophic pathway to determine whether the production or actions of GH or IGF-I are altered in these mice. We demonstrated that SOCS-2−/− mice do not have elevated GH levels and suffer no major pituitary dysmorphogenesis, and that SOCS-2-deficient embryonic fibroblasts do not have altered IGF-I signaling. Primary hepatocytes from SOCS-2−/− mice, however, did have moderately prolonged signal transducer and activator of transcription 5 signaling in response to GH stimulation. Furthermore, the deletion of SOCS-2 from mice also lacking signal transducer and activator of transcription 5b had little effect on growth, suggesting that the action of SOCS-2 may be the regulation of the GH signaling pathway.
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Cish and Socs2 decrease activation of STAT5.
“Cish and Socs2 decrease activation of STAT5 [67,68], which has both pro-proliferative (Cyclin D2) [69] and anti-apoptotic (Bcl-xl, Bcl6) targets, as well as targets involved in β-cell function (Figure 3) [56,70].”
From Expansion of β-cell mass in response to pregnancy (2010) · cites this paper as [68]
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References 60 · Cited by 166
Research works printed but not linked: 7
- Nicola, 2000, The suppressors of cytokine signaling (SOCS) proteins. Important feedback inhibitors of cytokine action., Exp Hematol, 28, 1105, 10.1016/S0301-472X(00)00525-7 · DOI
- Alexander, 1999, SOCS1 is a critical inhibitor of interferon γ signaling and prevents the potentially fatal neonatal actions of this cytokine., Cell, 98, 597, 10.1016/S0092-8674(00)80047-1 · DOI · Paper page
- Medrano, 1991, Growth hormone and insulin-like growth factor-I measurements in high growth (hg) mice., Genet Res, 58, 67, 10.1017/S0016672300029621 · DOI
- Nicoll, 1986, Similarities and differences among prolactin and growth hormone and their receptors., Am Zool, 26, 965, 10.1093/icb/26.4.965 · DOI
- Verdier, 1998, Proteasomes regulate erythropoietin receptor and signal transducer and activator of transcription 5 (STAT5) activation. Possible involvement of the ubiquitinated Cis protein., J Biol Chem, 273, 28185, 10.1074/jbc.273.43.28185 · DOI
- Waxman, 1995, Intermittent plasma growth hormone triggers tyrosine phosphorylation and nuclear translocation of a liver-expressed, Stat 5-related DNA binding protein. Proposed role as an intracellular regulator of male-specific liver gene transcription., J Biol Chem, 270, 13262, 10.1074/jbc.270.22.13262 · DOI
- Brysha, 2001, Suppressor of cytokine signaling-1 attenuates the duration of interferon gamma signal transduction in vitro and in vivo., J Biol Chem, 276, 22086, 10.1074/jbc.M102737200 · DOI · Paper page
- Authors
- Greenhalgh, C. J., Bertolino, P., Asa, S. L., Metcalf, D., Corbin, J. E., Adams, T. E., Davey, H. W., Nicola, N. A., Hilton, D. J., & Alexander, W. S.
- Affiliations
- The Royal Melbourne Hospital (AU)
- Centenary Institute (AU)
- University Health Network (CA)
- Commonwealth Scientific and Industrial Research Organisation (AU)
- AgResearch (NZ)
- ORCID
- Venue
- Molecular Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2002-06-01
- Volume
- 16
- Issue
- 6
- Pages
- 1394-1406
- ISSN
- 0888-8809 (ISSN-L)
- 1944-9917
- OpenAlex
- W2028944165
- Cited by
- 166
- References
- 60
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 1 · 2023: 7 · 2022: 3 · 2021: 5 · 2020: 4 · 2019: 6 · 2018: 3 · 2017: 9 · 2016: 8 · 2015: 7 · 2014: 4 · 2013: 7 · 2012: 7
- FWCI
- 8.46
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Australian Government
- National Institutes of Health
- Medical Research Council
- National Health and Medical Research Council
- National Cancer Institute (CA22556)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- SOCS2, STAT5B, growth promotion, growth hormone, IGF-1 signaling, pituitary development, hepatocytes, embryonic fibroblasts, growth hormone signaling
- MeSH terms
- Animals, Body Weight, Cell Line, DNA-Binding Proteins, Female, Growth, Insulin-Like Growth Factor I, Male, Milk Proteins, Phosphorylation, Pituitary Gland, Proteins, Repressor Proteins, RNA, Messenger, Skin, Growth Hormone, Blotting, Western, Signal Transduction, Trans-Activators, Gene Deletion, Mice, Knockout, Hepatocytes, STAT5 Transcription Factor, Suppressor of Cytokine Signaling Proteins, Mice
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